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The ocular surface may exhibit a wide variety of immunologic responses resulting in inflammation of the conjunctiva and cornea. In the Gell and Coombs classification system for various immunologic hypersensitivity reactions, 5 types of reactions are recognized. The major type I hypersensitivity reactions involving the conjunctiva are commonly referred to as allergic conjunctivitis. Diagnosis of allergic conjunctivitis is generally made by thorough history and careful clinical observation (see Clinical). The presence of an antigen starts the allergic cascade, and, thus, avoidance of the offending antigen is the primary behavioral modification for all types of allergic conjunctivitis. In other respects, management of allergic conjunctivitis varies somewhat according to the specific subtype. Allergic conjunctivitis can be treated with a variety of drugs, including topical antihistamines, mast cell stabilizers, nonsteroidal anti-inflammatory drugs, and corticosteroids (see Treatment). See the following for more information: Acute Hemorrhagic Conjunctivitis Atopic Keratoconjunctivitis Bacterial Conjunctivitis Emergent Treatment of Acute Conjunctivitis Epidemic Keratoconjunctivitis Giant Papillary Conjunctivitis Keratoconjunctivitis Sicca Neonatal Conjunctivitis Superior Limbic Keratoconjunctivitis Viral Conjunctivitis Immunologic reactions of conjunctiva and cornea Type I (immediate) hypersensitivity reactions occur when a sensitized individual comes in contact with a specific antigen. Immunoglobulin E (IgE) has a strong affinity for mast cells, and the cross-linking of 2 adjacent IgE molecules by the antigen triggers mast cell degranulation. The mast cells degranulation releases various preformed and newly formed mediators of the inflammatory cascade. Most notable of these inflammatory mediators are histamine, tryptase, chymase, heparin, chondroitin sulfate, prostaglandins, thromboxanes, and leukotrienes. These various inflammatory mediators, together with various chemotactic factors, result in an increase in vascular permeability and migration of eosinophils and neutrophils. This type I hypersensitivity reaction is the most common allergic response of the eye. These immune-derived reactions may be the underlying cause of various ocular conditions, such as cicatricial

pemphigoid and Mooren ulcer. Type III hypersensitivity reactions result in antigen-antibody immune complexes, which deposit in tissues and cause inflammation. A classic systemic type III reaction is the Arthus reaction, and ocular type III hypersensitivity reactions include Stevens-Johnson syndrome and marginal infiltrates of the cornea. These type III reactions can often induce a corneal immune (Wesley) ring that dissolves when the inflammatory reaction subsides. Type IV hypersensitivity reactions, also known as cell-mediated immunity, are interceded by T lymphocytes. This inflammatory cell-driven reaction is also referred to as delayed-type hypersensitivity, since its onset is generally after 48 hours, in contrast to the type I reaction, which is an immediate hypersensitivity. Type IV hypersensitivity reactions imply immunocompetence on the part of the individual since an intact immune system is required to mount the cellmediated response. Ocular examples of type IV hypersensitivity include phlyctenular keratoconjunctivitis, corneal allograft rejection, contact dermatitis, and drug allergies. Allergic conjunctivitis subtypes Allergic conjunctivitis may be divided into 5 major subcategories. Seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) are commonly grouped together. Vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC), and giant papillary conjunctivitis (GPC) constitute the remaining subtypes of allergic conjunctivitis. Early diagnosis and treatment will help prevent the rare complications that can occur with this disease. Prognosis Since allergic conjunctivitis generally clears up readily, the prognosis is favorable. Complications are very rare, with corneal ulcers or keratoconus occurring rarely. Although allergic conjunctivitis may commonly reoccur, it rarely causes any visual loss. Patient education Patients should make every attempt to identify the allergen causing the problem and to avoid the offending antigen. For patient education information, see the Eye and Vision Center, as well as Pinkeye, Eye

Allergies, and How to Instill Your Eyedrops.

Seasonal and perennial allergic conjunctivitis Since the conjunctiva is a mucosal surface similar to the nasal mucosa, the same allergens that trigger allergic rhinitis may be involved in the pathogenesis of allergic conjunctivitis. Common airborne antigens, including pollen, grass, and weeds, may provoke the symptoms of acute allergic conjunctivitis, such as ocular itching, redness, burning, and tearing. The main distinction between SAC and PAC, as implied by the names, is the timing of symptoms. Individuals with SAC typically have symptoms of acute allergic conjunctivitis for a defined period of time, that is, in spring, when the predominant airborne allergen is tree pollen; in summer, when the predominant allergen is grass pollen; or in fall, when the predominant allergen is weed pollen. Typically, persons with SAC are symptom-free during the winter months in cooler climates because of the decreased airborne transmission of these allergens. Seasonal allergic conjunctivitis can manifest itself through tear film instability and symptoms of eye discomfort during the pollen season. One study found that outside the pollen season, allergic inflammation did not cause permanent tear film instability.[1] In contrast, individuals with PAC may have symptoms that last the year round; thus, PAC may not be caused exclusively by seasonal allergens, although they may play a role. Other common household allergens, such as dust mite, cockroach dust, cigarette smoke, airborne allergens, and pet dander, may be responsible for the symptoms of PAC. Vernal keratoconjunctivitis VKC is a chronic bilateral inflammation of the conjunctiva, commonly associated with a personal and/or family history of atopy. More than 90% of patients with VKC exhibit one or more atopic conditions, such as asthma, eczema, or seasonal allergic rhinitis. Atopic keratoconjunctivitis AKC is a bilateral inflammation of conjunctiva and eyelids, which has a strong association with atopic dermatitis. It is also a type I hypersensitivity disorder with many similarities to VKC, yet AKC is distinct in a number of ways. In 1953, Hogan first described the association between atopic dermatitis and conjunctival inflammation.[2] He reported 5 cases of conjunctival inflammation in male patients with atopic dermatitis.[2] Atopic dermatitis is

a common hereditary disorder that usually has its onset in childhood; symptoms may regress with advancing age. Approximately 3% of the population is afflicted with atopic dermatitis, and, of these, approximately 25% have ocular involvement. Giant papillary conjunctivitis GPC is an immune-mediated inflammatory disorder of the superior tarsal conjunctiva. As the name implies, the primary finding is the presence of "giant" papillae, which are typically greater than 0.3 mm in diameter. A combination of type I and type IV hypersensitivity reactions may be responsible for the pathogenesis of GPC. It is believed that an antigen is present, in predisposed individuals, which stimulates the immunological reaction and the development of GPC. Prolonged mechanical irritation to the superior tarsal conjunctiva, of the upper lid, from any of a variety of foreign bodies may also be a contributing factor in GPC. Although contact lenses (hard and soft) are the most common irritant, ocular prostheses, extruded scleral buckles, and exposed sutures following previous surgical intervention may also precipitate GPC.

Allergic conjunctivitis occurs very frequently and is seen most commonly in areas with high seasonal allergens. VKC occurs predominantly in areas with tropical and temperate climates, such as the Mediterranean, the Middle East, and Africa. The limbal form of VKC commonly occurs in dark-skinned individuals from Africa and India. Sexual and age-related differences in incidence VKC has a significant male preponderance, typically affecting young males. The onset of VKC is generally in the first decade and persists for the first 2 decades. Symptoms usually peak prior to the onset of puberty and then subside.

Diagnosis of allergic conjunctivitis generally is made by taking a thorough history and by careful clinical observation. In seasonal and perennial allergic conjunctivitis, important features of the history include a personal or family history of atopic disease, such as allergic rhinitis, bronchial asthma, and/or atopic dermatitis. Perhaps the most important feature in the clinical history is the symptom of itching. Without itching, the diagnosis of

allergic conjunctivitis is suspect. Vernal keratoconjunctivitis With vernal keratoconjunctivitis (VKC), as with other allergic or type I hypersensitivity disorders, itching is the most important and most common symptom. Other commonly reported symptoms are photophobia, foreign body sensation, tearing, and blepharospasm. Ocular signs of VKC commonly are seen in the cornea and conjunctiva. In contrast to atopic keratoconjunctivitis (AKC), the eyelid skin usually is not involved. Atopic keratoconjunctivitis In AKC, unlike VKC, the symptoms are perennial. There may be seasonal variation, however, with worsening symptoms during winter months. The single most common symptom is bilateral itching of the eyelids, but watery discharge, redness, photophobia, and pain may be associated. Giant papillary conjunctivitis Primary symptoms in giant papillary conjunctivitis (GPC) are ocular itching with a mucoid or ropy discharge, very similar to that seen in VKC. Another symptom of GPC may be persistent foreign body sensations when using contact lenses, resulting in a decrease wear time and potential reduction in the visual acuity.

Physical Examination
Seasonal and perennial allergic conjunctivitis Classic signs of allergic conjunctivitis include injection of the conjunctival vessels as well as varying degrees of chemosis (conjunctival edema) and eyelid edema. The conjunctiva often has a milky appearance due to obscuration of superficial blood vessels by edema within the substantia propria of the conjunctiva. Edema is generally believed to be the direct result of increased vascular permeability caused by release of histamine from conjunctival mast cells. Vernal keratoconjunctivitis VKC may be subdivided into 2 varieties, as follows: palpebral and limbal. The classic conjunctival sign in palpebral VKC is the presence of giant papillae. The papillae most commonly occur on the superior tarsal conjunctiva; usually, the inferior tarsal conjunctiva is unaffected. Giant papillae assume a flattop appearance, which often is described as "cobblestone papillae." In severe cases, large papillae may cause mechanical ptosis (drooping eyelid).

A ropy mucous discharge may be present, which commonly is associated with tarsal papillae. Large numbers of eosinophils, indicating the presence of extended periods of inflammation, are present in the discharge. The limbal form of VKC commonly occurs in dark-skinned individuals, such as those from Africa or India. As the name implies, papillae tend to occur at the limbus, the junction between the cornea and the conjunctiva, and have a thick gelatinous appearance. They commonly are associated with multiple white spots (Horner-Trantas dots), which are collections of degenerated epithelial cells and eosinophils. Horner-Trantas dots rarely last longer than a week from their initial presentation. While corneal vascularization is rare, the cornea may be affected in a variety of ways. Punctate epithelial keratopathy (PEK) may result from the toxic effect of inflammatory mediators released from the conjunctiva. The appearance of PEK may be a precursor for the characteristic shield ulcer, which is pathognomonic of VKC. PEK can coalesce, resulting in frank epithelial erosion and forming into a shield ulcer, which is typically shallow with white irregular epithelial borders. Although the pathogenesis of a shield ulcer is not well understood, the major factor in promoting development may be chronic mechanical irritation from the giant tarsal papillae. Some evidence suggests that the major basic protein released from eosinophils may also promote ulceration. Another type of corneal involvement is vernal pseudogerontoxon, which is a degenerative lesion in the peripheral cornea resembling corneal arcus. Keratoconus may be seen in chronic cases, which may be associated with chronic eye rubbing. Atopic keratoconjunctivitis AKC may affect eyelid skin and lid margin, conjunctiva, cornea, and lens. Skin of the eyelids may exhibit eczematoid dermatitis with dry, scaly, and inflamed skin and the lid margins may show meibomian gland dysfunction and keratinization. Moreover, staphylococcal colonization of eyelid margins is very common in AKC and may result in blepharitis. Conjunctiva may show chemosis and typically a papillary reaction, which is more prominent in the inferior tarsal conjunctiva, in contrast to that seen in vernal keratoconjunctivitis. Hyperplasia of limbal regions may result in a gelatinous thickening, similar to the limbal variant of VKC, and, although rare, Horner-Trantas dots also may be present. Fibrosis or scarring of the conjunctiva may result in a shortened fornix or symblepharon formation with chronic inflammation. Corneal involvement ranges from PEK early in the course of the disease, to

neovascularization, stromal scarring, and possibly ulceration. There is also a strong association between herpes simplex viral keratitis and AKC. As seen in VKC patients, the chronic eye rubbing of the cornea may contribute to the development of keratoconus. Characteristic lenticular changes in AKC include anterior or posterior subcapsular cataract formation. These slow progressing lens opacities are usually bilateral and present in the second decade of life. There is some speculation that the long-term use of topical corticosteroids can also induce the lenticular changes later in life. Giant papillary conjunctivitis Examination of superior tarsal conjunctiva reveals the presence of large cobblestone papillae, which are generally 0.3 mm or greater in diameter. In his original description of GPC in 1977, Allansmith described 3 zones of superior tarsal conjunctiva.[3] Zone 1 is located closest to the fornix and is the most inferior portion of the tarsal conjunctiva seen when the upper eyelid is everted. Zone 3 is located closest to the eyelid margin. Zone 2 is located between zone 1 and zone 3. Papillae typically associated with soft contact lenses initially appears in zone 1 and progress toward zone 3, while those associated with rigid gas permeable contact lenses exhibit a reverse pattern, with zone 3 affected first. GPC associated with a localized irritant, such as an exposed suture or a filtering bleb, is typically localized to the area overlying these inciting lesions. Another clinical sign of GPC may be chronic bulbar conjunctival injection and inflammation due to prolonged and persistent use of contact lenses. Table. Major Differentiating Factors Between VKC and AKC Characteristics VKC AKC Age at onset Generally presents at a younger age than AKC Sex Males are affected No sex predilection preferentially. Seasonal variation Typically occurs Generally perennial during spring months Discharge Thick mucoid Watery and clear discharge discharge Conjunctival scarring Higher incidence of conjunctival scarring

Horner-Trantas dots

Horner-Trantas dots Presence of Hornerand shield ulcers Trantas dots is rare. are commonly seen. Corneal Not present Deep corneal neovascularization neovascularization tends to develop Presence of Conjunctival Presence of eosinophils in scraping reveals eosinophils is less conjunctival scraping eosinophils to a likely greater degree in VKC than in AKC

Approach Considerations

In seasonal and perennial allergic conjunctivitis, superficial conjunctival scrapings may help to establish the diagnosis by revealing eosinophils, but only in the most severe cases, since eosinophils are typically present in the deeper layers of the substantia propria of the conjunctiva. Therefore, the absence of eosinophils on conjunctival scraping does not rule out the diagnosis of allergic conjunctivitis. Many investigators have described measurement of tear levels of various inflammatory mediators, such as IgE, histamine, and tryptase, as indicators of allergic activity. Additionally, skin testing by an allergist may provide definitive diagnosis and pinpoint the offending allergen(s). In vernal keratoconjunctivitis (VKC), conjunctival scrapings of the superior tarsal conjunctiva and of Horner-Trantas dots show an abundance of eosinophils. Conjunctival scrapings of patients with atopic keratoconjunctivitis (AKC) may demonstrate the presence of eosinophils, although the number is not as significant as that seen in VKC. Additionally, free eosinophilic granules, which are seen in VKC, are not seen in AKC.

Histologic Findings
Vernal keratoconjunctivitis Conjunctival scrapings of the superior tarsal conjunctiva show an abundance of eosinophils. Conjunctival biopsy reveals that there are a large number of mast cells within the substantia propria. Histochemical analysis of mast cells, present in VKC, reveals neutral proteases tryptase and chymase. There is enhanced fibroblast proliferation, which leads to the deposition of collagen within the substantia propria and, as result, induces conjunctival thickening. B-cell and T-cell lymphocytes are present locally, which combine to produce IgE. Specific IgE and IgG as well as the inflammatory mediators histamine and tryptase have been isolated from tears of patients with VKC. Although

VKC is typically recognized as a type I hypersensitivity reaction, evidence has been found that supports some involvement of type IV hypersensitivity reaction. Atopic keratoconjunctivitis Conjunctival scrapings of patients with AKC may demonstrate the presence of eosinophils, although the number is not as significant as that seen in VKC. Additionally, free eosinophilic granules, which are seen in VKC, are not seen in AKC. Mast cells also may be found within the substantia propria of the conjunctiva in greater numbers. There is an increased amount of IgE in the tears of patients with AKC. Although AKC is typically recognized as a type I hypersensitivity reaction, evidence has been found that supports some involvement of type IV hypersensitivity reaction, as is the case in VKC. Giant papillary conjunctivitis Histologic findings in GPC consist of cellular infiltration of the conjunctiva by a number of cell types. Plasma cells, lymphocytes, mast cells, eosinophils, and basophils have been identified within the substantia propria. Mast cells also may be found in the epithelium. There is also elevated tear levels of immunoglobulin, especially IgE and tryptase also are elevated, as in AKC and VKC.

Approach Considerations
Avoidance of the offending antigen is the primary behavioral modification for all types of allergic conjunctivitis. In other respects, management of allergic conjunctivitis varies somewhat according to the specific subtype (ie, seasonal and perennial allergic conjunctivitis, vernal keratoconjunctivitis [VKC], atopic keratoconjunctivitis [AKC], giant papillary conjunctivitis[GPC]). Allergic conjunctivitis can be treated with a variety of medications, including topical antihistamines, mast cell stabilizers, nonsteroidal antiinflammatory drugs (NSAIDs), and corticosteroids. Surgical intervention may be indicated in severe cases of VKC or AKC. See the following for more information: Acute Hemorrhagic Conjunctivitis Atopic Keratoconjunctivitis Bacterial Conjunctivitis Emergent Treatment of Acute Conjunctivitis

Epidemic Keratoconjunctivitis Giant Papillary Conjunctivitis Keratoconjunctivitis Sicca Neonatal Conjunctivitis Superior Limbic Keratoconjunctivitis Viral Conjunctivitis

Management of Seasonal and Perennial Allergic Conjunctivitis

Pharmacologic intervention may be necessary to help alleviate the symptoms of acute allergic conjunctivitis. Various classes of medication may be effective against the symptoms of acute allergic conjunctivitis; each is directed at a specific point in the inflammatory and allergic cascade. Artificial tears Artificial tear substitutes provide a barrier function and help to improve the first-line defense at the level of conjunctival mucosa. These agents help to dilute various allergens and inflammatory mediators that may be present on the ocular surface, and they help flush the ocular surface of these agents. Antihistamines Systemic and/or topical antihistamines may be prescribed to relieve acute symptoms due to interaction of histamine at ocular H1 and H2 receptors. While systemic antihistamines often relieve ocular allergic symptoms, patients may experience systemic adverse affects, such as drowsiness and dry mouth. Topical antihistamines competitively and reversibly block histamine receptors and relieve itching and redness but only for a short time. These medications do not affect other proinflammatory mediators, such as prostaglandins and leukotrienes, which remain uninhibited. A number of topical antihistamines are available, including epinastine (Elestat) and azelastine (Optivar). Both are potent antihistamines that have a rapid onset and are effective in relieving the signs and symptoms of allergic conjunctivitis. Vasoconstrictors Vasoconstrictors are available either alone or in conjunction with antihistamines to provide short-term relief of vascular injection and redness. Common vasoconstrictors include naphazoline, phenylephrine, oxymetazoline, and tetrahydrozoline. Generally, the common problem with vasoconstrictors is that they may cause rebound conjunctival injection and inflammation. These pharmacologic agents are ineffective against severe

ocular allergies and against other more severe forms of allergic conjunctivitis, such as atopic and vernal disease. Mast cell stabilizers Mast cell stabilizers have a mechanism of action that is unclear. They may aid in the phosphorylation of a 78,000-d protein that terminates secretion of mast cell granules; they may increase calcium influx into the cell preventing membrane changes; and/or they may reduce membrane fluidity prior to mast cell degranulation. The end result is a decrease in degranulation of mast cells, which prevents release of histamine and other chemotactic factors that are present in the preformed and newly formed state. Note that mast cell stabilizers do not relieve existing symptoms and are to be used on a prophylactic basis to prevent mast cell degranulation with subsequent exposure to the allergen. Therefore, they need to be used long term in conjunction with various other classes of medications. Common mast cell stabilizers include cromolyn sodium and lodoxamide (Alomide). Alcaftadine (Lastacaft), bepotastine (Bepreve), olopatadine (Patanol), nedocromil (Alocril), and ketotifen (Zaditor) are mast cell stabilizers and inhibit histamine release. NSAIDs Nonsteroidal anti-inflammatory drugs (NSAIDs) act on the cyclooxygenase metabolic pathway and inhibit production of prostaglandins and thromboxanes. They have no role in blocking mediators formed by the lipoxygenase pathway, such as leukotrienes. Common NSAIDs that are approved for allergic indications include ketorolac tromethamine (Acular). Corticosteroids Corticosteroids remain among the most potent pharmacologic agents used in the treatment of chronic ocular allergy. They act at the first step of the arachidonic acid pathway by inhibiting phospholipase, which is responsible for converting membrane phospholipid into arachidonic acid. By preventing the formation of arachidonic acid, corticosteroids effectively block both cyclooxygenase and lipoxygenase pathways, in contrast to NSAIDs, which act only on the cyclooxygenase pathway. Corticosteroids do have limitations, including ocular adverse effects, such as delayed wound healing, secondary infection, elevated intraocular pressure, and formation of cataract. In addition, the anti-inflammatory and immunosuppressive affects are nonspecific. As a rule, topical steroids should be prescribed only for a short period of time and for severe cases that do not respond to conventional therapy.

Corticosteroids exist in various forms and potencies. Relatively weak steroids, such as rimexolone, medrysone, and fluorometholone, tend to have less potency in the eye, with fewer ocular adverse effects. In contrast, agents such as prednisolone acetate are more potent and have a higher incidence of adverse effects. Loteprednol etabonate (Lotemax 0.05% and Alrex 0.02%), a steroid, is rapidly metabolized once it enters the anterior chamber of the eye. Therefore, it is extremely useful in treating ocular surface and superficial corneal inflammations. Alrex has a specific indication for ocular allergy and has been shown in clinical studies to have fewer ocular adverse effects. Immunotherapy Immunotherapy is a mainstay in the systemic management of allergies. Traditionally, immunotherapy is delivered via subcutaneous injection. However, sublingual (oral) immunotherapy (SLIT) is gaining momentum among allergists. Numerous articles have analyzed the effects of SLIT on allergic conjunctivitis. Preliminary indications are that SLIT may have a moderate effect on the signs and symptoms of allergic conjunctivitis, but further analysis is necessary.[4] A 2012 study confirmed that SLIT may significantly reduce symptoms in children with grass pollenallergic rhinoconjunctivitis. The preparation studied had significant effects on allergen-specific antibodies and was well tolerated. [5]

Management of Vernal Keratoconjunctivitis

Multiple pharmacologic agents may be used to provide varying degrees of relief. Mucolytic agents, such as acetylcysteine, may help minimize the discharge and provide temporary relief. Vasoconstrictors may reduce hyperemia but are not effective in severe cases on a long-term basis. Moreover, the long-term use of vasoconstrictors may have a rebound effect, leaving the eye untreatably injected. Similarly, topical antihistamines have no significant long-term benefit. Mast cell stabilizers, with antihistamine effects, are perhaps the mainstay of treatment of VKC and are safe for long-term use. However, topical corticosteroids generally become necessary for most patients with significant symptoms. Because of their potential adverse effects, topical steroids should be prescribed at the lowest effective concentration and for the shortest duration possible. A pulsed-therapy steroid regimen is generally recommended every 2 hours for the first week followed by a rapid taper; this may be repeated if symptoms recur. Systemic steroids may be used but generally are not necessary for moderate cases of VKC.

Several reports have shown that topical cyclosporine (Restasis), indicated for the use in keratoconjunctivitis sicca, may be effective in reducing some of the signs and symptoms of VKC without adverse effects. Oral aspirin has been shown to be effective in relieving some of the inflammation associated with allergy. Treatment of corneal shield ulcer may require antibiotic-steroid ointments. Surgical treatment Severe cases of corneal shield ulcer may require superficial keratectomy to promote epithelial regeneration. Generally, shield ulcers are chronic conditions that are often refractory to conventional therapy. There have been reports of excimer laser phototherapeutic keratectomy (PTK) being used to remove fibrin deposits on the Bowman layer and theoretically facilitate epithelial healing. Other surgical procedures, such as cryoablation of giant papillae or surgical removal of papillae with mucosal grafting, generally are not required, but they may be helpful in extremely advanced cases. Remember that since VKC is a self-limited disease, extensive reconstructive surgery may not have an acceptable risk-benefit ratio.

Management of Atopic Keratoconjunctivitis

Treatment of patients with AKC, similar to that for VKC, consists of controlling the environment and avoiding allergens. These patients may require topical and systemic medications to ultimately provide real symptomatic relief. As with VKC, topical vasoconstrictors and antihistamines may provide very limited, short-term relief; they are not the mainstay of treatment. The use of topical mast cell stabilizers and topical corticosteroids provide significant relief of symptoms. Mast cell stabilizers have to be used for several weeks before taking effect; in the interim, topical steroids used in a pulsed fashion may help to control symptoms. Systemic antihistamines that are specific for H1 histamine receptors have been found to be helpful. Systemic steroids rarely are required, except in cases of vision-threatening complications. Systemic cyclosporine, which has been shown to be effective in the treatment of atopic dermatitis, has also shown promise in controlling ocular inflammation in AKC. Postulated mechanism of action is inhibition of the ability of T lymphocytes to produce interleukin 2 (IL-2), which is responsible for recruiting and activating new T cells. However, as with any systemic therapy, adverse effects may be significant; therefore, monitoring of serum levels and renal function is essential.

Concomitant herpes simplex virus infection should be treated with either topical or oral antiviral agents as needed. A subset of patients with recalcitrant and debilitating AKC may benefit from plasmapheresis, as was described by Aswad in 2 patients, one of whom had hyperimmunoglobulinemia E.[6] Penetrating keratoplasty may be undertaken in cases of severe corneal scarring or thinning. However, great attention to control ocular surface inflammation is required.

Management of Giant Papillary Conjunctivitis

Resolution of symptoms and restoration of functional use of contacts lenses or ocular prosthetics are the main goals of treatment for GPC. Although removal of the responsible foreign body is the definitive treatment, and that may be appropriate for exposed sutures or scleral buckles, complete discontinuation of contact lenses or ocular prosthetics may be met with some degree of resistance from patients. Fortunately, contact lens wear does not need to be completely discontinued to minimize the symptoms of GPC. Significant reduction in the signs and symptoms may be achieved by changing the contact lens care routine. Disinfecting solutions that contain chemical preservatives should be discontinued. Converting from soft dailywear contact lenses to disposable or daily-disposable soft contact lenses may prevent the accumulation of proteinaceous deposits, which may be the antigenic stimulus for GPC. Rigid gas-permeable contact lenses may provide further relief from symptoms if disposable lenses do not provide adequate response. This relief is due to the decreased proclivity of the rigid gas-permeable contact lenses to develop adherent deposits and coatings. Pharmacologic treatment of GPC includes the use of mast cell stabilizers, topical corticosteroids, and antihistamines, in a manner similar to that in the other immunologic conjunctival disorders discussed previously. As always, care must be taken when using topical corticosteroids; a pulsed regimen is recommended to minimize adverse reactions.

Prevention of Allergic Conjunctivitis

Seasonal and perennial allergic conjunctivitis Avoidance of the offending antigen is the primary behavioral modification; specific testing by an allergist will identify the responsible allergen(s) and help the individual to establish ways to avoid the allergen. Contact reactions caused by medications or cosmetics are also treated best by

avoidance. Vernal keratoconjunctivitis As with most type I hypersensitivity disorders, allergen avoidance should be emphasized as the first-line treatment. Although permanent relocation to a cooler climate is not feasible in many cases, it remains a very effective therapy for VKC. Maintenance of an air-conditioned environment and control of dust particles at home and work may also be beneficial. Local measures, such as cold compresses and periodic instillation of artificial tears, have also been shown to provide temporary relief.

Medication Summary
Allergic conjunctivitis can be treated with a variety of drugs. These include topical antihistamines, mast cell stabilizers, nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids. As always, care must be taken when using topical corticosteroids; pulsed regimen is recommended to minimize adverse reactions.

Antihistamine, Ophthalmic
Class Summary These agents act by competitive inhibition of histamine at the H1 receptor. They block the effects of endogenously released histamine.
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Emedastine difumarate (Emadine) This agent is a relatively selective H-receptor antagonist for topical administration. The 0.05% ophthalmic solution contains 0.884 mg/mL of emedastine difumarate.
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Levocabastine Levocabastine is a selective histamine H1 receptor antagonist. The active ingredient in this product is 0.54 mg levocabastine hydrochloride.
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Epinastine (Elestat) A direct histamine-1 receptor antagonist, epinastine does not penetrate the blood-brain barrier and therefore should not induce adverse CNS effects. It is indicated for symptoms due to allergic conjunctivitis.
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Azelastine ophthalmic (Optivar) Azelastine competes with H1-receptor sites on effector cells and inhibits release of histamine and other mediators involved in allergic response.
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Bepotastine besilate ophthalmic solution (Bepreve) Bepotastine besilate is a topically active antihistamine that directly antagonizes H1-receptors and inhibits release of histamine from mast cells. It is indicated for itching associated with allergic conjunctivitis.
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Alcaftadine ophthalmic (Lastacaft) An H1-receptor antagonist indicated for prevention of itching associated with allergic conjunctivitis, alcaftadine inhibits histamine release from mast cells, decreases chemotaxis, and inhibits eosinophil activation. It is available as a 0.25% ophthalmic solution.

Mast Cell Stabilizers

Class Summary Mast cell stabilizers inhibit the degeneration of sensitized mast cells when exposed to specific antigens by inhibiting the release of mediators from the mast cells. These agents block calcium ions from entering the mast cell. Olopatadine is a relatively selective H1 receptor antagonist and inhibitor of histamine release from mast cells.[7, 8]
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Lodoxamide tromethamine (Alomide) Lodoxamide is a mast cell stabilizer. The active ingredient in this product is 1.78 mg lodoxamide tromethamine.
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Olopatadine (Patanol, Pataday) Olopatadine is a relatively selective H1 receptor antagonist and inhibitor of histamine release from mast cells. The active ingredient of Patanol is 1.11 mg olopatadine hydrochloride; Pataday is 2.22 mg olopatadine hydrochloride.
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Ketotifen (Zaditor, Alaway) Ketotifen is an over-the-counter (OTC) antihistamine eye drop. It is a noncompetitive H1-receptor antagonist and mast cell stabilizer. This agent inhibits release of mediators from cells involved in hypersensitivity

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Nedocromil ophthalmic (Alocril) Nedocromil interferes with mast cell degranulation, specifically with release of leukotrienes and platelet activating factor.

Class Summary Corticosteroids have both anti-inflammatory (glucocorticoid) and salt retaining (mineralocorticoid) properties. Glucocorticoids have profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.
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Loteprednol etabonate (Lotemax, Alrex) This agent decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability. It is a topical ester steroid eye drop that poses a decreased risk of glaucoma. It is available in 0.2% and 0.5% concentrations.

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Class Summary The mechanism of action of NSAIDs is believed to be through inhibition of the cyclooxygenase enzyme that is essential in the biosynthesis of prostaglandins, which results in vasoconstriction, decrease in vascular permeability and leukocytosis, and a decrease on intraocular pressure.
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Ketorolac tromethamine (Acular, Acuvail) A member of the pyrrolo-pyrrole group of NSAIDs, ketorolac inhibits prostaglandin synthesis by decreasing activity of the enzyme cyclooxygenase, which results in decreased formation of prostaglandin precursors; in turn, this results in reduced inflammation. The active ingredient is 0.5% ketorolac tromethamine.

Konjungtivitis vernalis adalah konjungtivitis akibat reaksi hipersensitivitas (tipe I) yang mengenai kedua mata dan bersifat rekuren. (1)

Terdapat dua bentuk utama konjngtivitis vernalis (yang dapat berjalan bersamaan), yaitu : 1. Bentuk palpebra terutama mengenai konjungtiva tarsal superior. Terdapat pertumbuhan papil yang besar ( Cobble Stone ) yang diliputi sekret yang mukoid. Konjungtiva tarsal bawah hiperemi dan edem, dengan kelainan kornea lebih berat dari tipe limbal. Secara klinik, papil besar ini tampak sebagai tonjolan besegi banyak dengan permukaan yang rata dan dengan kapiler di tengahnya. 2. Bentuk Limbal hipertrofi papil pada limbus superior yang dapat membentuk jaringan hiperplastik gelatin, dengan Trantas dot yang merupakan degenarasi epitel kornea atau eosinofil di bagian epitel limbus kornea, terbentuknya pannus, dengan sedikit eosinofil.(1)

Konjungtivitis vernal terjadi akibat alergi dan cenderung kambuh pada musim panas. Konjungtivitis vernal sering terjadi pada anak-anak, biasanya dimulai sebelum masa pubertas dan berhenti sebelum usia 20.(4)

Perubahan struktur konjungtiva erat kaitannya dengan timbulnya radang insterstitial yang banyak didominasi oleh reaksi hipersensitivitas tipe I dan IV. Pada konjungtiva akan dijumpai hiperemia dan vasodilatasi difus, yang dengan cepat akan diikuti dengan hiperplasi akibat proliferasi jaringan yang menghasilkan pembentukan jaringan ikat yang tidak terkendali. Kondisi ini akan diikuti oleh hyalinisasi dan menimbulkan deposit pada konjungtiva sehingga terbentuklah gambaran cobblestone. Jaringan ikat yang berlebihan ini akan memberikan warna putih susu kebiruan sehingga

konjungtiva tampak buram dan tidak berkilau. Proliferasi yang spesifik pada konjungtiva tarsal, oleh von Graefe disebut pavement like granulations. Hipertrofi papil pada konjungtiva tarsal tidak jarang mengakibatkan ptosis mekanik dan dalam kasus yang berat akan disertai keratitis serta erosi epitel kornea.

Limbus konjungtiva juga memperlihatkan perubahan akibat vasodilatasi dan hipertropi yang menghasilkan lesi fokal. Pada tingkat yang berat, kekeruhan pada limbus sering menimbulkan gambaran distrofi dan menimbulkan gangguan dalam kualitas maupun kuantitas stem cells limbus. Kondisi yang terakhir ini mungkin berkaitan dengan konjungtivalisasi pada penderita

keratokonjungtivitis dan di kemudian hari berisiko timbulnya pterigium pada usia muda . Di samping itu, juga terdapat kista-kista kecil yang dengan cepat akan mengalami degenerasi.(3)

Tahap awal konjungtivitis vernalis ditandai oleh fase prehipertrofi. Dalam kaitan ini, akan tampak pembentukan neovaskularisasi dan pembentukan papil yang ditutup oleh satu lapis sel epitel dengan degenerasi mukoid dalam kripta di antara papil serta pseudomembran milky white. Pembentukan papil ini berhubungan dengan infiltrasi stroma oleh sel-sel PMN, eosinofil, basofil, dan sel mast.

Hasil penelitian histopatologik terhadap 675 konjungtivitis vernalis mata yang dilakukan oleh Wang dan Yang menunjukkan infiltrasi limfosit dan sel plasma pada konjungtiva. Prolifertasi limfosit akan membentuk beberapa nodul limfoid. Sementara itu, beberapa granula eosinofilik dilepaskan dari sel eosinofil, menghasilkan bahan sitotoksik yang berperan dalam kekambuhan konjungtivitis. Dalam

penelitian tersebut juga ditemukan adanya reaksi hipersensitivitas. Tidak hanya di konjungtiva bulbi dan tarsal, tetapi juga di fornix, serta pada beberapa kasus melibatkan reaksi radang pada iris dan badan siliar .

Fase vaskular dan selular dini akan segera diikuti dengan deposisi kolagen, hialuronidase, peningkatan vaskularisasi yang lebih mencolok, serta reduksi sel radang secara keseluruhan. Deposisi kolagen dan substansi dasar maupun seluler mengakibatkan terbentuknya deposit stone yang terlihat secara nyata pada pemeriksaan klinis. Hiperplasia jaringan ikat meluas ke atas membentuk giant papil bertangkai dengan dasar perlekatan yang luas. Kolagen maupun pembuluh darah akan mengalami hialinisasi. Epiteliumnya berproliferasi menjadi 510 lapis sel epitel yang edematous dan tidak beraturan. Seiring dengan bertambah besarnya papil, lapisan epitel akan mengalami atrofi di apeks sampai hanya tinggal satu lapis sel yang kemudian akan mengalami keratinisasi.

Pada limbus juga terjadi transformasi patologik yang sama berupa pertumbuhan epitel yang hebat meluas, bahkan dapat terbentuk 30-40 lapis sel (acanthosis). Horner-Trantas dot`s yang terdapat di daerah ini sebagian besar terdiri atas eosinofil, debris selular yang terdeskuamasi, namun masih ada sel PMN dan limfosit. (3)

Pasien umumnya mengeluh tentang gatal yang sangat dan bertahi mata berserat-serat. Biasanya terdapat riwayat keluarga alergi (demam jerami, eczema, dan lain-lain) dan kadang-kadang pada pasien muda juga. Konjungtiva tampak putih seperti susu, dan terdapat banyak papilla halus di konjungtiva tarsalis inferior. Konjungtiva palpebra superior sering memiliki papilla raksasa mirip batu kali. Setiap papil raksasa berbentuk poligonal, dengan atap rata, dan mengandung berkas kapiler.

Gambar 1. konjungtivitis vernalis. Papilla batu bata di konjungtiva tarsalis superior.(5)

Mungkin terdapat tahi mata berserabut dan pseudomembran fibrinosa (tanda Maxwell-Lyons). Pada beberapa kasus, terutama pada orang negro turunan Afrika, lesi paling mencolok terdapat di limbus, yaitu pembengkakan gelatinosa (papillae). Sebuah pseudogerontoxon (arcus) sering terlihat pada kornea dekat papilla limbus. Bintik-bintik Tranta adalah bintik-bintik putih yang terlihat di limbus pada beberapa pasien dengan konjungtivitis vernalis selama fase aktif dari penyakit ini. Sering tampak mikropannus pada konjungtivitis vernal palpebra dan limbus, namun pannus besar jarang dijumpai. Biasanya tidak timbul parut pada konjungtiva kecuali jika pasien telah menjalani krioterapi, pengangkatan papilla, iradiasi, atau prosedur lain yang dapat merusak konjungtiva. (2)

Diagnosis ditegakkan berdasarkan gejala dan hasil pemeriksaan mata.(4) Pemeriksaan laboratorium yang dilakukan berupa kerokan konjungtiva untuk mempelajari gambaran sitologi. Hasil pemeriksaan menunjukkan banyak eosinofil dan granula-granula bebas eosinofilik. Di samping itu, terdapat basofil dan granula basofilik bebas.(3)

Karena konjungtivitis vernalis adalah penyakit yang sembuh sendiri, perlu diingat bahwa medikasi yang dipakai terhadap gejala hanya memberi hasil jangka pendek, berbahaya jika dipakai jangka panjang.(2) Opsi perawatan konjungtivitis vernalis berdasarkan luasnya symptom yang muncul dan durasinya. Opsi perawatan konjungtivitis vernalis yaitu : 1. Tindakan Umum Dalam hal ini mencakup tindakan-tindakan konsultatif yang membantu mengurangi keluhan pasien berdasarkan informasi hasil anamnesis. Beberapa tindakan tersebut antara lain: Menghindari tindakan menggosok-gosok mata dengan tangan atau jari tangan, karena telah terbukti dapat merangsang pembebasan mekanis dari mediator-mediator sel mast. Di samping itu, juga untuk mencegah superinfeksi yang pada akhirnya berpotensi ikut menunjang terjadinya glaukoma sekunder dan katarak. Pemakaian mesin pendingin ruangan berfilter; Menghindari daerah berangin kencang yang biasanya juga membawa serbuksari; Menggunakan kaca mata berpenutup total untuk mengurangi kontak dengan alergen di udara terbuka. Pemakaian lensa kontak justru harus dihindari karena lensa kontak akan membantu retensi allergen; Kompres dingin di daerah mata; Pengganti air mata (artifisial). Selain bermanfaat untuk cuci mata juga berfungsi protektif karena membantu menghalau allergen; Memindahkan pasien ke daerah beriklim dingin yang sering juga disebut sebagai climatotherapy.

2. -

Terapi topikal Untuk menghilangkan sekresi mucus, dapat digunakan irigasi saline steril dan mukolitik seperti asetil sistein 10%20% tetes mata. Dosisnya tergantung pada kuantitas eksudat serta beratnya gejala. Dalam hal ini, larutan 10% lebih dapat ditoleransi daripada larutan 20%. Larutan alkalin seperti 1-2% sodium karbonat monohidrat dapat membantu melarutkan atau mengencerkan musin, sekalipun tidak efektif sepenuhnya. dekongestan antihistamin NSAID (Non-Steroid Anti-Inflamasi Drugs) Untuk konjungtivitis vernalis yang berat, bisa diberikan steroid topikal prednisolone fosfat 1%, 6-8 kali sehari selama satu minggu. Kemudian dilanjutkan dengan reduksi dosis sampai ke dosis terendah yang dibutuhkan oleh pasien tersebut. Bila sudah terdapat ulkus kornea maka kombinasi antibiotik steroid terbukti sangat efektif. Antihistamin antibakteri Siklosporin Stabilisator sel mast seperti Sodium kromolin 4% dan Lodoksamid 0,l%.

3. -

Terapi Sistemik Pada kasus yang lebih parah, bisa juga digunakan steroid sistemik seperti prednisolone asetat, prednisolone fosfat, atau deksamethason fosfat 23 tablet 4 kali sehari selama 12 minggu. Satu hal yang perlu diingat dalam kaitan dengan pemakaian preparat steroid adalah gunakan dosis serendah mungkin dan sesingkat mungkin. Antihistamin, baik lokal maupun sistemik, dapat dipertimbangkan sebagai pilihan lain,

karena kemampuannya untuk mengurangi rasa gatal yang dialami pasien. Apabila dikombinasi dengan vasokonstriktor, dapat memberikan kontrol yang memadai pada kasus yang ringan atau memungkinkan reduksi dosis.

4. -

Tindakan Bedah Berbagai terapi pembedahan, krioterapi, dan diatermi pada papil raksasa konjungtiva tarsal kini sudah ditinggalkan mengingat banyaknya efek samping dan terbukti tidak efektif, karena dalam waktu dekat akan tumbuh lagi. (3,6)

Konjungtivitis vernalis adalah konjungtivitis akibat reaksi hipersensitivitas (tipe I) yang mengenai kedua mata dan bersifat rekuren. Konjungtivitis vernal terjadi akibat alergi dan cenderung kambuh pada musim panas. Konjungtivitis vernal sering terjadi pada anak-anak, biasanya dimulai sebelum masa pubertas dan berhenti sebelum usia 20. Gejala yang spesifik berupa rasa gatal yang hebat, sekret mukus yang kental dan lengket, serta hipertropi papil konjungtiva. Tanda yang spesifik adalah Trantas dots dan coble stone. Terdapat dua bentuk dari konjungtivitis vernalis yaitu bentuk palbebra dan bentuk limbal.

Konjungtivitis vernalis pada umumnya tidak mengancam penglihatan, namun dapat menimbulkan rasa tidak enak. Penyakit ini biasanya sembuh sendiri tanpa diobati. Namun tetap dibutuhkan perawatan agar tidak terjadi komplikasi dan menurunkan tingkat ketidaknyamanan dari pasien.

Perawatan yang dapat diberikan menghindari menggosok-gosok mata, kompres dingin di daerah mata, memakai pengganti air mata, memakai obat tetes seperti asetil sistein, antihistamin, NSAID, steroid, stabilisator sel

mast, dll; obat oral (seperti antihistamin dan steroid), dan pembedahan.
Anatomi & Fisiologi Konjungtiva Konjungtiva adalah membran mukosa yang transparan dan tipis yang membungkus permukaan posterior kelopak mata (konjungtiva palpebralis) dan permukaan anterior sklera (konjungtiva bulbaris). Konjungtiva bersambungan dengan kulit pada tepi kelopak (persambungan mukokutan) dan dengan epitel kornea limbus.2 Konjungtiva mengandung kelenjar musin yang dihasilkan oleh sel goblet. Musin bersifat membasahi bola mata terutama kornea. Konjungtiva terdiri atas tiga bagian, yaitu : Konjungtiva tarsal yang menutupi tarsus, konjungtiva tarsal sukar digerakkan dari tarsus. Konjungtiva bulbi menutupi sklera dan mudah digerakkan dari sklera di bawahnya. Konjungtiva fornises atau forniks konjungtiva yang merupakan tempat peralihan konjungtiva tarsal dengan konjungtiva bulbi. Konjungtiva bulbi dan forniks berhubungan dengan sangat longgar dengan jaringan di bawahnya sehingga bola mata mudah bergerak.1

Gambar 1. Anatomi Konjungtiva11 Secara histologis, konjungtiva terdiri atas lapisan : 3. Lapisan epitel konjungtiva, terdiri dari dua hingga lima lapisan sel epitel silinder

bertingkat, superficial dan basal. Lapisan epitel konjungtiva di dekat limbus, di atas karankula, dan di dekat persambungan mukokutan pada tepi kelopak mata terdiri dari sel-sel epitel skuamosa. 4. Sel-sel epitel supercial, mengandung sel-sel goblet bulat atau oval yang mensekresi mukus. Mukus mendorong inti sel goblet ke tepi dan diperlukan untuk dispersi lapisan air mata secara merata diseluruh prekornea. Sel-sel epitel basal berwarna lebih pekat daripada sel-sel superficial dan di dekat limbus dapat mengandung pigmen. 5. Stroma konjungtiva, dibagi menjadi : Lapisan adenoid (superficial) Lapisan adenoid mengandung jaringan limfoid dan dibeberapa tempat dapat mengandung struktur semacam folikel tanpa sentrum germinativum. Lapisan adenoid tidak berkembang sampai setelah bayi berumur 2 atau 3 bulan. Hal ini menjelaskan mengapa konjungtivitis inklusi pada neonatus bersifat papiler bukan folikuler dan mengapa kemudian menjadi folikuler. Lapisan fibrosa (profundus) Lapisan fibrosa tersusun dari jaringan penyambung yang melekat pada lempeng tarsus. Hal ini menjelaskan gambaran reksi papiler pada radang konjungitiva. Lapisan fibrosa tersusun longgar pada bola mata. 6. Kelenjar air mata asesori (kelenjar Krause dan wolfring), yang struktur dan fungsinya mirip kelenjar lakrimal, terletak di dalam stroma. Sebagian besar kelenjar krause berada di forniks atas, dan sedikit ada di forniks bawah. Kelenjar wolfring terletak ditepi atas tarsus atas.2 2.2 Definisi Konjungtivitis vernal adalah peradangan konjungtiva bilateral dan berulang (recurrence) yang khas, dan merupakan suatu reaksi alergi. Penyakit ini juga dikenal sebagai catarrh musim semi dan konjungtivitis musiman atau konjungtivitis musim kemarau. Sering terdapat pada musim panas di negeri dengan empat musim, atau sepanjang tahun di negeri tropis (panas).2,7 2.3 Etiologi dan Predisposisi Konjungtivitis vernal terjadi akibat reaksi hipersensitivitas tipe I yang mengenai

kedua mata, sering terjadi pada orang dengan riwayat keluarga yang kuat alergi.7,8 Mengenai pasien usia muda 3-25 tahun dan kedua jenis kelamin sama. Biasanya pada laki-laki mulai pada usia dibawah 10 tahun. Penderita konjungtivitis vernal sering menunjukkan gejala-gejala alergi terhadap tepung sari rumput-rumputan.1 Reaksi hipersentsitivitas memiliki 4 tipe reaksi seperti berikut: Tipe I : Reaksi Anafilaksi Di sini antigen atau alergen bebas akan bereaksi dengan antibodi, dalam hal ini IgE yang terikat pada sel mast atau sel basofil dengan akibat terlepasnya histamin. Keadaan ini menimbulkan reaksi tipe cepat. Tipe II : reaksi sitotoksik Di sini antigen terikat pada sel sasaran. Antibodi dalam hal ini IgE dan IgM dengan adanya komplemen akan diberikan dengan antigen, sehingga dapat mengakibatkan hancurnya sel tersebut. Reaksi ini merupakan reaksi yang cepat menurut Smolin (1986), reaksi allografi dan ulkus Mooren merupakan reaksi jenis ini. Tipe III : reaksi imun kompleks Di sini antibodi berikatan dengan antigen dan komplemen membentuk kompleks imun. Keadaan ini menimbulkan neurotrophichemotactic factor yang dapat menyebabkan terjadinya peradangan atau kerusakan lokal. Pada umumnya terjadi pada pembuluh darah kecil. Pengejawantahannya di kornea dapat berupa keratitis herpes simpleks, keratitis karena bakteri. (stafilokok, pseudomonas) dan jamur. Reaksi demikian juga terjadi pada keratitis Herpes simpleks. Tipe IV : Reaksi tipe lambat Pada reaksi hipersensitivitas tipe I, II dan III yang berperan adalah antibodi (imunitas humoral), sedangkan pada tipe IV yang berperan adalah limfosit T atau dikenal sebagai imunitas seluler. Limfosit T peka ( sensitized T lymphocyte) bereaksi dengan antigen, dan menyebabkan terlepasnya mediator (limfokin) yang jumpai pada reaksi penolakan pasca keratoplasti, keraton- jungtivitis flikten, keratitis Herpes simpleks dan keratitis diskiformis.14 2.4 Manifestasi Klinis Gejala yang mendasar adalah rasa gatal, manifestasi lain yang menyertai meliputi mata berair, sensitif pada cahaya, rasa pedih terbakar, dan perasaan seolah ada benda asing yang masuk. Penyakit ini cukup menyusahkan, muncul berulang, dan sangat membebani aktivitas penderita sehingga menyebabkan ia tidak dapat beraktivitas normal.6

Terdapat dua bentuk klinik, yaitu : Bentuk palpebra, terutama mengenai konjungtiva tarsal superior. Terdapat pertumbuhan papil yang besar (cobble stone) yang diliputi sekret yang mukoid. Konjungtiva tarsal bawah hiperemi dan edema, dengan kelainan kornea lebih berat dibanding bentuk limbal. Secara klinik papil besar ini tampak sebagai tonjolan bersegi banyak dengan permukaan yang rata dan dengan kapiler ditengahnya.

Gambar 2. Konjungtivitis vernal bentuk palpebral12 Bentuk limbal, hipertrofi papil pada limbus superior yang dapat membentuk jaringan hiperplastik gelatin, dengan Trantas dot yang merupakan degenerasi epitel kornea atau eosinofil di bagian epitel limbus kornea, terbentuknya pannus, dengan sedikit eosinofil.1

Gambar 3. Konjungtivitis vernal bentuk limbal13 2.5 Patofisiologi Pada bentuk palpebral, jaringan epitel membesar pada beberapa area dan menular ke area lainnya. Kadangkala, eosinofil (warna kemerahan) tampak kuat di antara sel-sel jaringan epitel. Perubahan yang menonjol dan parah terjadi pada substansi propria (jaringan urat). Pada tahap awal jaringan terinfiltrasi dengan limfosit, sel plasma, eosinofil, dan basofil. Sejalan dengan perkembangan penyakit, semakin banyak sel yang berakumulasi dan kolagen baru terbentuk, sehingga menghasilkan bongkol-bongkol besar pada jaringan

yang timbul dari lempeng tarsal. Terkait dengan perubahan-perubahan tersebut adalah adanya pembentukan pembuluh darah baru dalam jumlah yang banyak. Peningkatan jumlah kolagen berlangsung cepat dan menyolok.6 Pada bentuk limbal terdapat perubahan yang sama, yaitu: perkembangbiakan jaringan ikat, peningkatan jumlah kolagen, dan infiltrasi sel plasma, limfosit, eosinofil dan basofil ke dalam stroma. Penggunaan jaringan yang dilapisi plastik yang ditampilkan melalui mikroskopi cahaya dan elektron dapat memungkinkan beberapa observasi tambahan. Basofil sebagai ciri tetap dari penyakit ini, tampak dalam jaringan epitel sebagaimana juga pada substansi propria. Walaupun sebagian besar sel merupakan komponen normal dari substansi propia, namun tidak terdapat jaringan epitel konjungtiva normal.6 Walaupun karakteristik klinis dan patologi konjungtivitis vernal telah digambarkan secara luas, namun patogenesis spesifik masih belum dikenali.6 2.6 Pemeriksaan Penunjang Pada eksudat konjungtiva yang dipulas dengan Giemsa terdapat banyak eosinofil dan granula eosinofilik bebas.9 Pada pemeriksaan darah ditemukan eosinofilia dan peningkatan kadar serum IgE.3 Pada konjungtivitis vernal, terdapat sebagian besar sel yang secara rutin tampak dalam jaringan epitel. Pengawetan yang lebih baik adalah menggunakan glutaraldehyde, lapisan plastik, dan ditampilkan pada media sehingga dapat memungkinkan untuk menghitung jumlah sel ukuran 1 berdasarkan jenis dan lokasinya. Jumlah rata-rata sel per kubik milimeter tidak melampaui jumlah normal. Diperkirakan bahwa peradangan sel secara maksimum seringkali berada dalam kondisi konjungtiva normal. Jadi, untuk mengakomodasi lebih banyak sel dalam proses peradangan konjungtivitis vernal, maka jaringan akan membesar dengan cara peningkatan jumlah kolagen dan pembuluh darah. Jaringan tarsal atas yang abnormal ditemukan dari empat pasien konjungtivitis vernal yang terkontaminasi dengan zat imun, yaitu: dua dari empat pasien mengandung spesimen IgA-, IgG-, dan IgE- secara berlebih yang akhirnya membentuk sel plasma. Sel-sel tersebut tidak ditemukan pada konjungtiva normal dari dua pasien lainnya. Kandungan IgE pada air mata yang diambil dari sampel serum 11 pasien konjungtivitis vernal dan 10 subjek kontrol telah menemukan bahwa terdapat korelasi yang signifikan antara air mata dengan level kandungan serum pada kedua mata. Kandungan IgE

pada air mata diperkirakan muncul dari serum kedua mata, kandungan IgE dalam serum (1031ng/ml) dan pada air mata (130ng/ml) dari pasien konjungtivitis vernal melebihi kandungan IgE dalam serum (201ng/ml) dan pada air mata (61ng/ml) dari orang normal. Butiran antibodi IgE secara spesifik ditemukan pada air mata lebih banyak daripada butiran antibodi pada serum. Selain itu, terdapat 18 dari 30 pasien yang memiliki level antibodi IgG yang signifikan yang menjadi butiran pada air matanya. Orang normal tidak memiliki jenis antibodi ini pada air matanya maupun serumnya. Hasil pengamatan ini menyimpulkan bahwa baik IgE- dan IgG- akan menjadi perantara mekanisme imun yang terlibat dalam patogenesis konjungtivitis vernal, dimana sistesis lokal antibodi terjadi pada jaringan permukaan mata. Kondisi ini ditemukan negatif pada orang-orang yang memiliki alergi udara, tetapi pada penderita konjungtivitis vernal lebih banyak berhubungan dengan antibodi IgG dan mekanisme lainnya daripada antibodi IgE. Kandungan histamin pada air mata dari sembilan pasien konjungtivitis vernal (38ng/ml) secara signifikan lebih tinggi daripada kandungan histamin air mata pada 13 orang normal (10ng/ml, P<0.05). Hal ini sejalan dengan pengamatan menggunakan mikroskopi elektron yang diperkirakan menemukan tujuh kali lipat lebih banyak sel mastosit dalam substantia propia daripada dengan pengamatan yang menggunakan mikroskopi cahaya. Sejumlah besar sel mastosit ini terdapat pada air mata dengan level histamin yang lebih tinggi. Kikisan konjungtiva pada daerah-daerah yang terinfeksi menunjukkan adanya banyak eosinofil dan butiran eosinofilik. Ditemukan lebih dari dua eosinofil tiap pembesaran 25x dengan sifat khas penyakit (pathognomonic) konjungtivitis vernal. Tidak ditemukan adanya akumulasi eosinofil pada daerah permukaan lain pada level ini.6 2.7 Diferensial Diagnosis Walaupun secara prinsip konjungtivitis vernal sangat berbeda dengan trakhom dan konjungtivitis demam rumput, namun seringkali gejalanya membingungkan dengan dua penyakit tersebut. Trakhom ditandai dengan banyaknya serabut-serabut sejati yang terpusat, sedangkan pada konjungtivitis vernal jarang tampak serabut sejati. Pada trakhom, eosinofil tidak tampak pada kikisan konjungtiva maupun pada jaringan, sedangkan pada konjungtivitis vernal, eosinofil memenuhi jaringan. Trakhom meninggalkan parut-parut pada tarsal, sedangkan konjungtivitis vernal tidak, kecuali bila terlambat ditangani. Tanda konjungtivitis demam rumput adalah edema, sedangkan tanda konjungtivitis

vernal adalah infiltrasi selular. Demam rumput memiliki karakteristik sedikit eosinofil, tidak ada sel mastosit pada jaringan epitel, tidak ada peningkatan sel mastosit pada substantia propria, dan tidak terdapat basofil, sedangkan konjungtivitis vernal memiliki karakteristik adanya tiga serangkai, yaitu: sel mastosit pada jaringan epitel, adanya basofil, dan adanya eosinofil pada jaringan.6

Tabel 1. Diagnosis banding Trakoma, Konjungtivitis folikularis, Konjungtivitis vernal.1

Trakoma Gambaran lesi


Konjungitvitis vernal Nodul lebar datar dalam susunan stone konjungtiva atas dan diselimuti

folikularis (kasus dini) papula kecil atau Penonjolan bercak (folikel merah bertaburan merah-muda Pada teratur

dengan bintik putih-kuning pucat tersusun cobble trakoma). tarsal dan seperti pada bawah, konjungtiva butir sagu) (kasus deretan beads tarsal parut,

lanjut) granula (menyerupai terutama Ukuran lesi Lokasi lesi atas Penonjolan konjungtivatarsal besar lesi Penonjolan

lapisan susu

Penonjolan tarsus palpebra;

besar atau

konjungtiva tarsal atas dan kecil kornea-panus, infiltrasi abu-abu bawah tarsal dan dan bawah

terutama tipe

teristimewa lipatan retrotarsal konjungtiva

bawah konjungtiva tarsus forniks terlibat, forniks tarsus bebas. Tipe limbus atau bulbus; limbus terlibat forniks bebas, konjungtiva tarsus bebas (tipe campuran lazim) tarsus tidak terlibat

pembuluh tarsus terlibat.

tidak terlibat.

Tipe sekresi Pulasan

Kotoran air berbusa atau Mukoid frothy pada stadium lanjut. purulen Kerokan epitel dari Kerokokan konjungtiva dan kornea tidak memperlihatkan

atau Bergetah, seperti susu Eosinofil karakteristik konstan sekresi


dan pada

ekfoliasi, karakteristik (Koch-Weeks, MoraxAxenfeld, mikrokokus kataralis stafilokokkus,

proliferasi, inklusi seluler.

Penyulit atau

pneumokokkus) Kornea: panus, kekeruhan Kornea: ulkus Kornea: kornea, xerosis, kornea kornea


kornea (tipe limbal)


Komplikasi Dapat menimbulkan keratitis epitel atau ulkus kornea superfisial sentral atau

parasentral, yang dapat diikuti dengan pembentukan jaringan sikatriks yang ringan. Penyakit ini juga dapat menyebabkan penglihatan menurun. Kadang-kadang didapatkan panus, yang tidak menutupi seluruh permukaan kornea. Perjalanan penyakitnya sangat menahun dan berulang, sering menimbulkan kekambuhan terutama di musim panas.5 2.9 Penatalaksanaan Biasanya penyakit ini akan sembuh sendiri. Tetapi medikasi yang dipakai terhadap gejala hanya memberikan hasil jangka pendek, karena dapat berbahaya jika dipakai untuk jangka panjang. Penggunaan steroid berkepanjangan ini harus dihindari karena bisa terjadi infeksi virus, katarak, hingga ulkus kornea oportunistik. Farmakologi Natrium kromoglikat 2% topikal dapat diberikan 4 kali sehari untuk mencegah degranulasi Anti histamin dan steroid sistemik dapat diberikan pada kasus yang berat. Cromolyn topical adalah agen profilaktik yang baik untuk kasus sedang sampai berat. Bila Antibiotik dapat diberikan untuk mencegah infeksi sekunder disertai dengan sikloplegik. Anti-radang non-steroid yang lebih baru, seperti kerolac dan iodoxamine, cukup bermanfaat sel mast.

tidak ada hasil dapat diberikan radiasi, atau dilakukan pengangkatan giant papil.

mengurangi gejala. Non Farmakologi Penderita diusahakan untuk menghindari menggosok-gosok karena akan menyebabkan iritasi berlanjut. Kompres dingin dapat juga digunakan untuk menghilangkan edema. Selain itu, tidur di tempat ber AC dapat menyamankan pasien. Lebih baik apabila penderita pindah ke tempat beriklim sejuk dan lembab.

2.10 Prognosis Kondisi ini dapat terus berlanjut dari waktu ke waktu, dan semakin memburuk selama

musim-musim tertentu.8